Generally, the WT1 protein-derived cancer antigen peptide is a partial peptide derived from human WT1 protein consisting of 449 amino acids (SEQ ID NO: 2), and is specifically a peptide consisting of 8-12 amino acids or a dimer thereof. It is presented to a major histocompatibility complex (MHC) class I antigen, and includes a peptide which is antigen-recognized by cytotoxic T cell (cytotoxic T-lymphocyte, hereinafter to be referred to as CTL). MHC in human is called human leukocyte antigen (HLA).
Among the WT1 protein-derived partial peptides, a partial peptide consisting of 9 amino acids and shown by the sequence WT1126-134 peptide Arg-Met-Phe-Pro-Asn-Ala-Pro-Tyr-Leu (SEQ ID NO: 1), and a modified peptide, wherein partial amino acid(s) is(are) modified (modified peptide), have been reported to be useful as peptides that bind to HLA to induce CTL (see patent documents 1-3, non-patent document 1).
A cancer antigen protein and a cancer antigen peptide, which are generally used for cancer vaccine, are administered with an adjuvant (immunopotentiating agent) in many cases to induce CTL more efficiently.
However, it is often difficult to maintain stability, particularly stability in water, of the formulations comprising these proteins and peptides. Therefore, the formulations removed water by freeze-drying are generally selected. Nevertheless, freeze-dried formulations are disadvantageous from the aspects of production and cost, and also require an operation when in use such as adding water and the like.
In view of the above, it is significant to develop a stable aqueous liquid composition that enables easy combination of a cancer antigen protein or cancer antigen peptide with various adjuvants depending on the object of use.
As for the stabilization of a liquid, a freeze-dried formulation containing citric acid or methionine as a stabilizer of gonadotropin (see patent document 4), a formulation containing methionine as a stabilizer of G-CSF (see patent document 5), and a formulation having pH 4 or below and containing succinic acid or tartaric acid as a stabilizer of G-CSF (see patent document 6) are disclosed.
Furthermore, a formulation containing, as stabilizers of modified factor VIII polypeptide in solution, (1) pH adjuster to fall within the range of about 4.0-about 8.0, (2) an antioxidant, and (3) calcium salt, magnesium salt is disclosed (see patent document 7). In addition, a formulation with improved stability, which contains a physiologically active medicament, methionine and a novel erythropoiesis stimulating protein is disclosed (see patent document 8).
However, a stable aqueous liquid composition containing a partial peptide having the sequence shown by SEQ ID NO: 1 or a modified peptide thereof, which is of interest in the present invention, has not been known.